Understanding how neuroblasts and neurons polarize is a fundamental problem in neurodevelopment. We propose to study this problem in C. elegans with a focus on how polarity is established along the C. elegans anterior/posterior (A/P) axis. C. elegans has been an important model for the nervous system development. In both C. elegans and the spinal cord, the same molecules guide migrating axons along the dorsal/ventral and A/P axes. Wnt glycoproteins, for example, guide axons toward the anterior in both organisms. In C. elegans, Wnts are the main regulators not only of axon guidance, but also of neuroblast and neuronal polarity. We propose to define the common mechanisms that Wnts use to regulate these two processes. In addition, disregulation of Wnt-pathway components contributes to many forms of cancer. Understanding the mechanisms of Wnt regulation and signaling has potential implications for spinal cord repair and cancer. PUBLIC HEALTH RELEVANCE: All cells exhibit polarity. Polarity is particularly important during nervous system development, where the proper establishment of polarity is essential for neuroblasts to divide to produce neurons, for neurons to migrate and for axons to find their synaptic targets. We propose to study how neuronal polarity is regulated in model organism C. elegans by the family of secreted Wnt glycoproteins.